AbstractGenetically engineered, Cre/LoxP‐conditional mouse models of cancer are designed to investigate the genetic contributors of tumorigenesis and are well suited to assess therapeutic treatment responses. The capacity to serially visualize tumor burden in a noninvasive fashion would greatly strengthen their applications. We report the generation of a bioluminescent reporter strain that allows monitoring of tumor development in preexisting conditional mouse tumor models. We demonstrate that, in a Cre‐dependent glioblastoma multiforme model, tumor initiation and progression is readily monitored over time and that luminescent output is related to tumor volume. Our results show that this reporter strain may be combined with various Cre/loxP mouse tumor models to allow for noninvasive longitudinal monitoring of tumor growth and therapeutic response in vivo. genesis 47:659–666, 2009. © 2009 Wiley‐Liss, Inc.